海藻糖BMP-2基因激活双功能涂层对骨质疏松大鼠种植体骨整合作用的研究

Osteoporosis, a common bone metabolic disease with low bone formation ability and high expression of inflammatory factors, impacts the effect of oral implant prosthesis. Surface modification of oral implants has been considered as an effective method to improve osseointegration in osteoporosis patients. Current surface modification methods mainly resolve the problem from a single aspect by increasing the osteogenic activity of titanium implants or preparing antibacterial coatings. However, the effects of these methods were comparatively limited. In light of the feature of osteoporosis on implant prosthesis and based on our previous study, we preferentially choose high transfection efficiency lentivirus bone morphogenetic protein 2(BMP-2) gene and trehalose to modify titanium implant surface. With the freeze-drying protection and anti-inflammatory function of trehalose,the effect of freeze-drying on the bioactivity of lentivirus BMP-2 gene and the mechanism of anti-inflammatory will be explored. Based on these, trehalose and BMP-2 gene activited coating will be prepared by freeze-drying method and the dual function of the coating on osteogenic activity and inflammatory factors expression will be evaluated. Finally, the effect of dual functional coating on osseointegration of titanium implants in osteoporosis rats will be investigated. With this project, we will find more evidence for further application of trehalose BMP-2 gene activited dual functional coating. The successful preparation of titanium implants with dual functional coating will be a more feasible and effective new method for improvement of osseointegration in osteoporosis patients.

骨质疏松症是一种常见的影响种植修复效果的骨代谢性疾病，其特点是成骨能力减弱和炎症因子表达增高。种植体表面改性是提高骨质疏松状态下骨整合的有效方法。目前的改性技术多从改善种植体表面生物活性或制备抗菌涂层等单一方面入手，提高骨整合的效果有限。针对骨质疏松症影响种植修复的特点，课题组在前期工作基础上选用高转染效率的慢病毒骨形成蛋白2（BMP2）基因和海藻糖进行种植体表面改性。利用海藻糖的冻干保护作用，探索冻干对慢病毒BMP2基因生物活性的影响；同时利用海藻糖的抗炎作用，在深入探讨其抗炎机制的基础上，通过冻干法制备钛表面海藻糖BMP2基因激活涂层，评价涂层对成骨活性和炎症因子表达的双重作用，并观察其对骨质疏松症大鼠种植体骨整合的影响。本研究将为海藻糖BMP2基因激活双功能涂层的研制和应用提供理论依据，而双功能涂层种植体的成功制备，可望为改善骨质疏松症患者种植修复的效果探索一条更加行之有效的新方法。

种植体表面改性是提高骨质疏松状态下骨整合的有效方法。在骨质疏松状态下，机体成骨能力减弱和炎症因子表达增高，本项目通过制备海藻糖冻干慢病毒BMP-2双功能涂层改善种植体的骨整合能力。海藻糖是天然的生物活性大分子的冻干保护剂，课题成功构建了高转染效率的慢病毒BMP-2载体，并利用海藻糖作为冻干保护剂，制备了冻干BMP-2重组基因慢病毒载体；冻干后的BMP-2慢病毒载体生物学活性未受影响，有效促进了骨髓基质细胞的成骨分化；在此基础上，将冻干海藻糖BMP-2制备成TiO2表面改性种植体涂层，延缓了BMP-2的释放，相比于单纯BMP-2涂层的TiO2表面改性种植体，促进了种植体的骨整合；同时发现冻干海藻糖BMP-2基因涂层不仅抑制了炎症因子的表达，同时促进了骨髓基质细胞的分化，在体内实验中促进了骨质疏松大鼠种植体骨整合和结合强度。本研究将为海藻糖BMP2基因激活双功能涂层的研制和应用提供理论依据，而双功能涂层种植体的成功制备，为改善骨质疏松症患者种植修复的效果探索出一条更加行之有效的新方法。